Early assessment time points (e.g., postnatal day (PND) 11/21) tended to be more sensitive than later time points (e.g., PND 60). These results demonstrate that data generated
using the current guideline DNT study protocol are useful in providing points of departure for risk assessments. The results of these studies also affirm the importance of evaluating a spectrum of behavioral and neuropathological endpoints, in both young and adult animals, to improve the detection of the potential for a chemical to cause developmental neurotoxicity. Published by Elsevier Inc.”
“Acute lymphoblastic leukemia (ALL) harboring the t(4;11) translocation is associated with a very poor prognosis; innovative treatment strategies are required to improve SRT1720 manufacturer the current 5-year survival rate of 30-40%. Interferon beta (IFN beta) has shown promise in the treatment of both solid and hematologic malignancies, although the short half-life and toxicity associated with high doses have limited its clinical utility. To overcome these limitations, we investigated the effect of continuous, gene transfer-mediated delivery of IFN beta using adeno-associated virus (AAV)-mediated expression, on ALL cells with the t(4; 11) translocation. We found that this method of IFN beta delivery resulted in complete remission of leukemia in a murine model. However, leukemic cells eventually became
resistant to IFN beta and relapse was observed. Activation of NF-kappa B was identified as a mechanism for IFN beta resistance, and inhibition of E2 conjugating inhibitor NF-kappa B activity Succinyl-CoA in resistant cells sensitized cells to IFN beta. IFN beta combined with agents that inhibit NF-kappa B could have therapeutic potential in the treatment of children with mixed lineage leukemia subtype
ALL. Leukemia (2010) 24, 806-812; doi: 10.1038/leu.2010.2; published online 4 February 2010″
“Use of the anti-acne drug, Accutane (R) (ACC) (isotretinoin, 13-cis-retinoic acid), has been associated with neuropsychiatric events ranging from depression in animal models to depression and suicide ideation in humans. Our studies, however, have consistently indicated few effects on measures of depression in male and female rats. Still, the comorbidity of depression and anxiety suggests that anxiety assessments in ACC-treated rats could be informative. Such assessments must be balanced with measures of activity since drug-induced activity alterations may impact the expression of anxiety-like behaviors. Here, Sprague-Dawley rats (n = 15/sex/dose) were gavaged daily with 0 (soy oil), 7.5, or 30 mg/kg/day ACC beginning on postnatal day (PND) 59. Blood ACC levels similar to humans taking recommended ACC doses are produced by 7.5 mg/kg/day. Short-term activity was assessed in open fields prior to ACC treatment (PND 51) and again at PNDs 129 and 164 and in a complex environment at PNDs 66 and PND 184.